Vitamin D (VitD) and vitamin K (VitK), essential fat-soluble micronutrients regulating bone homeostasis and gut microbiota, exhibit high global deficiency rates. Infant formulas demonstrate low bioavailability of VitD3 and VitK1. This study investigated how medium- and long-chain triacylglycerols (MLCTs, MLCT1 vs MLCT2) with distinct MLCT concentrations (25% vs 40%) affect VitD3/VitK1 bioavailability using integrated in vitro-in vivo models. In vitro digestion revealed that 40% MLCT2 significantly enhanced free fatty acid release (52.81%, P < 0.05) and bioaccessibility (VitD3: 54.37%; VitK1: 67.14%, P < 0.05) compared to MLCT1. Pharmacokinetic analysis demonstrated that 40% MLCT2 achieved superior bioavailability (AUC: VitD3 3880.26 μg/L×h; VitK1 710.12 μg/L×h) and metabolic efficacy (serum 25OHVitD3: (34.72 ± 10.85) ng/mL; VitK1: (27.28 ± 2.5) ng/mL) compared to 25% MLCT2. Long-term animal studies showed 40% MLCT2 administration significantly improved bone mineral density ((0.10±0.02) g/cm³, P < 0.001) and enriched Bacteroidetes and Eubacterium_coprostanoligenes_group - taxa linked to vitamin metabolism. These findings establish MLCTs as advanced lipid carriers to combat VitD/VitK deficiencies, offering transformative strategies for nutrient delivery systems with enhanced bioavailability.

Although human milk fat substitute (HMFS) has been wildly applied in infant formula (IF), there are still some differences in fat composition between human milk and IF, which is extremely attributed to the phospholipid composition. We therefore designed a human milk phospholipid substitute (HMPS), and investigated its nutritional outcomes on brain development using C57BL/6J mice. Results showed that HMPS improved mice’s cognitive behavior and dendritic development compared to soybean phospholipids and no-phospholipid diets. Based on the lipidomics, we revealed that these beneficial outcomes were potentially associated with the increased biosynthesis of N-acylethanolamines, phosphatidylethanolamine (PE), and ether PE, and the decreased metabolism of diacylglycerol and hexosylceramide in brain. It was further found in Kyoto Encyclopedia of Genes and Genomes analysis that glycerophospholipid metabolic pathway participated in the improvement of HMPS on mice’s neurodevelopment. In conclusion, this study demonstrated that HMPS improves mice’s neurodevelopment, and the glycerophospholipid metabolic pathway plays a major role in this beneficial result, and provided evidence for future application of HMPS in commercial IF.

Diet, as the core means of obtaining nutrients in the human body, plays a key role in maintaining a state of health and influencing the development of diseases. High fat diets (HFD) can cause hyperlipidaemia, obesity, type 2 diabetes, hypertension, cardiovascular disease, and other diseases. Dietary interventions have emerged as effective adjunctive therapies, especially dietary fatty acids and antioxidant intake can improve dyslipidaemia induced by HFD. Here, to explore the effects of unsaturated fatty acid-rich diets supplemented with antioxidants on lipid and fatty acid metabolism in high-fat rats, 40 Sprague-Dawley rats (half male and half female) were divided into 4 groups and fed with basal diet (C), basal diet supplemented with 12.7% mixed oil (MO), mixed oil plus VE (50 mg/kg) (MOV), and mixed oil plus VE (50 mg/kg) and propolis (30 mg/kg) (MOVP) for 6 weeks. The unsaturated fatty acid-enriched mixed oil was added to meet the requirements of dietary fatty acid ratio: 27% saturated fatty acid (SFA), 32.5% monounsaturated fatty acid (MUFA), and 40.5% polyunsaturated fatty acid (PUFA) (n-6 PUFA/n-3 PUFA = 1:1). Blood lipid biochemical index as well as the profile of a total of fatty acids were determined in heart, liver, brain, muscle, subcutaneous fat, and kidney. HFD increased the level of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) and decreased the lever of high-density lipoprotein-cholesterol (HDL-C) in rat plasma and tissues. MO group increased contents of most unsaturated fatty acids, especially n-3 PUFAs, in all these organs, and a synergistic elevation in these unsaturated fatty acids was further observed in combination with VE and propolis. Hence, the addition of antioxidants could protect unsaturated fatty acids against oxidation, thereby reducing the onset and progression of diseases associated with an HFD.